This invention relates to a method and apparatus for nanoscale synthesis of chemical compounds in continuous flow systems with controlled and regulated reaction conditions. More particularly, this invention relates to a modular multi-component nanoscale system with interchangeable nanoreactors, where the nanoreactors are used in tandem, series, or individually for nanoscale synthesis and is adaptable to prepare up to milligram quantities of desired compounds by adding additional reactor units.
Organic and inorganic reactions are usually conducted in reaction vessels that typically hold between 0.5 and 1000 mL of reactants in a research laboratory to commercial reactors holding more than 1000 L. Complex inorganic and organic compounds, e.g., drugs, monomers, organometallic compounds, semi-conductors, polymers, peptides, oligonucleotides, polynucleotides, carbohydrates, amino acids, and nucleic acids belong to a class of materials having significant diagnostic, medicinal and commercial importance. However, the systems necessary to carry out and prepare or synthesize these complex materials are inefficient, wasteful and often times require reagent quantities far in excess of what is available. This is especially the case in those instances where milliliter to liter or larger quantities are involved.
The production of these complex materials requires a versatile system that can handle different reaction and separatory schemes. Most synthesizers provide only for a single type of reactor, e.g., electrochemical, catalytic, solid phase support, enzyratic, photochemical, or hollow chamber. These systems are exemplified by the following:
U.S. Pat. No. 4, 517,338 (Urdea) teaches a system for sequencing amino acids with similar reaction zones having an internal diameter (I.D.) of a 0.1 to 1.0 cm;
U.S. Pat. No. 4,960,566 (Mochida) describes an automatic analyzer and process for serial processing of reaction tubes of a common design;
U.S. Pat. No. 4,362,699 (Verlander et al.) teaches high pressure peptide synthesizers and uses a plurality of reservoirs that communicate via a switching valve to a reactor 90;
U.S. Pat. No. 4,458,066 (Caruthers et al.) teaches an amino acid synthesizer with reactor column 10 including a solid silica gel approximately 1 ml. volume in size; and
U.S. Pat. No. 4,728,502 (Hamill) relates to a stacked disk amino acid sequencer.
The present invention provides an Integrated Chemical Synthesis (ICS) system that is modular in design and is capable of nanoliter (nanoscale) size or microscale size processing via continuous flow or batch operation. The modular nature of the system allows for the use of one or more of the same type of reactors, or a variety of different types of reactors, preferably having nanoscale capacity, but capable of using microscale reactors. The nanoscale reactors of the present invention are capable of being used individually, together, and interchangeably with one another and can be of the thermal electrochemical catalytic, enzymatic, photochemical, or hollow chamber type. The modular nature of the system, component parts, e.g., the reactors, flow channels, sensors, detectors, temperature control units, allows easy addition, replacement and/or interchangeability of the component parts.
Other generic components that are included within this invention are flow components (ie., pumps, valves, manifolds, etc.), mixers, separation chambers, heat transfer elements, resistance, ultrasonic or electromagnetic radiation (U.V., I.R., or visible) sources, heaters and/or analyzers. The components are assembled on a support system, e.g., a chip or board, to form a complete nanoscale system and then replicated many times to produce the synthesizer of the desired scale.
The advantage of a nanoscale synthesizer is better yields of products with less waste and disposal problems because of better control of reaction variables. For example, a cylindrical (capillary) reactor with an internal diameter of 100 mm, 1 cm long, with a cell volume of about 0.08 mL. At a linear flow velocity of 0.1 cm/s, the transit time through the cell would be 10 s, and the volume flow would 8xc3x9710xe2x88x923 mL/s. If conversion of a 1 M solution reactant was complete in this time, then the output of the cell would be 8 nmol product/s. For a product with a molecular weight of 100 g/mol, this would be equivalent to about 3 mg/h or 25 g/year of product. Thus, a bench-sized reactor consisting of 1000 nanoscale synthesis units would produce 69 g/day, while a larger reactor with 176,000 units would be needed to produce 11 kg/year. Considerable yields would require, however, the use of a large number of parallel systems, and to justify their use, the unit cost of each must be very small and their assembly fast and easy.
As a result of the present nanoscale synthesis modular system, the problems of inefficiency, lack of versatility, down-time, reagent/reactant waste and excessive cost have been overcome.
Accordingly, the present invention provides a nanoscale system for synthesizing chemical compounds that is easily upgraded to produce larger quantities of compounds if desired. The system of the present invention can also synthesize compounds under a variety of process conditions, e.g., uniform temperature in a continuous flow reactor under high pressure, non-uniform temperatures and high pressure.
One aspect of the present invention is the use of nanoscale size reactors for combinatorial synthesis, since nanoreactor and nanosystem design allows for the production of small quantities of pure materials for testing.
In accordance with another aspect of the present invention, a modular multicomponent system is provided. The system, e.g. a kit, provides a reaction system capable of handling a variety of reactions by using a reactor unit having a reaction chamber with an I.D. of less than about 0.01 mm up to about 1 mm, and more preferably 0.1 mm-100 mm, most preferably 0.1 mm to 10 mm. Specifically, a modular xe2x80x9cchipxe2x80x9d type reactor unit is formed by applying a photo-resist layer onto an upper surface of a SiO2 or Si substrate and forming a reactor design thereon. The reactor design is developed and etched with acid to form a reactor chamber having an internal diameter of less than 100 mm. The chamber is covered and the unit mounted on an assembly board containing fluid conveying channels, with fastening means, to provide for flow to and from the reactor chamber.
In accordance with another aspect of the present invention, a modular multicomponent system containing a plurality of interchangeable reaction vessels, alike or different, in parallel or series, and capable of handling reaction volumes of at least 0.1 nL or from about 0.01 nL up to about 10 mL, and more preferably 1 nL--1 mL is provided.
In yet another aspect of the present invention, a system capable of regulating extreme conditions (e.g., supercritical temperatures and pressures) is provided and therefore avoids potential explosions and, provides a reliable method for heat dissipation.
These and other features, aspects and objects will become more apparent in view of the following detailed description, examples and annexed drawings.